دورية أكاديمية
Deglutarylation of glutaryl-CoA dehydrogenase by deacylating enzyme SIRT5 promotes lysine oxidation in mice.
| العنوان: | Deglutarylation of glutaryl-CoA dehydrogenase by deacylating enzyme SIRT5 promotes lysine oxidation in mice. |
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| المؤلفون: | Bhatt DP; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA; Department of Cell Biology and Physiology, Washington University in St. Louis, St. Louis, Missouri, USA., Mills CA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA., Anderson KA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA; Sarah W. Stedman Nutrition and Metabolism Center, Duke University School of Medicine, Durham, North Carolina, USA; Departments of Medicine and Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA., Henriques BJ; Biosystems and Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal; Departmento de Química e Bioquimica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal., Lucas TG; Biosystems and Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal; Departmento de Química e Bioquimica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal., Francisco S; Biosystems and Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal; Departmento de Química e Bioquimica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal., Liu J; Departments of Medicine and Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA., Ilkayeva OR; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA; Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition, Duke University School of Medicine, Durham, North Carolina, USA., Adams AE; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA., Kulkarni SR; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA., Backos DS; Computational Chemistry and Biology Core Facility, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Major MB; Department of Cell Biology and Physiology, Washington University in St. Louis, St. Louis, Missouri, USA., Grimsrud PA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA; Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition, Duke University School of Medicine, Durham, North Carolina, USA., Gomes CM; Biosystems and Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal; Departmento de Química e Bioquimica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal., Hirschey MD; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA; Sarah W. Stedman Nutrition and Metabolism Center, Duke University School of Medicine, Durham, North Carolina, USA; Departments of Medicine and Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA; Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition, Duke University School of Medicine, Durham, North Carolina, USA. Electronic address: matthew.hirschey@duke.edu. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2022 Apr; Vol. 298 (4), pp. 101723. Date of Electronic Publication: 2022 Feb 12. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Glutaryl-CoA Dehydrogenase*/metabolism , Lysine*/metabolism , Sirtuins*/metabolism, Animals ; Mice ; Oxidation-Reduction ; Protein Processing, Post-Translational ; Tryptophan/metabolism |
| مستخلص: | A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be nonenzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH) and show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal that glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We also demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a feedback loop model within the lysine/tryptophan oxidation pathway in which glutaryl-CoA is produced, in turn inhibiting GCDH function via glutaryl modification of GCDH lysine residues and can be relieved by SIRT5 deacylation activity. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | R01 DK115568 United States DK NIDDK NIH HHS; U42 OD010924 United States OD NIH HHS; R01 AG045351 United States AG NIA NIH HHS; UL1 TR001082 United States TR NCATS NIH HHS; P30 DK124723 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: amino acid; cell metabolism; glutaryl-CoA dehydrogenase (GCDH); glutarylation; liver; lysine metabolism; posttranslational modification (PTM); sirtuin; sirtuin 5 (SIRT5) |
| المشرفين على المادة: | 0 (SIRT5 protein, mouse) 8DUH1N11BX (Tryptophan) EC 1.3.8.6 (Glutaryl-CoA Dehydrogenase) EC 3.5.1.- (Sirtuins) K3Z4F929H6 (Lysine) |
| تواريخ الأحداث: | Date Created: 20220214 Date Completed: 20220426 Latest Revision: 20220531 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8969154 |
| DOI: | 10.1016/j.jbc.2022.101723 |
| PMID: | 35157847 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2022.101723 |